Endometriosis and infertility: Monthly case report
Case: A 32-year old woman without prior pregnancies presented for initial consultation. She was diagnosed via laparoscopy at age 16 with mild endometriosis, and was started on OCPs. The laparoscopy was only diagnostic. By age 28, she had undergone 3 additional laparoscopies, all describing increasingly severe endometriosis, and all 3 involving fulguration of endometriotic surface lesions on fallopian tubes, ovaries, crucial ligaments and peritoneum in the cul-de-sac. In her final laparoscopy (4th) she, however, also for the first time demonstrated a small endometrioma, which was laparoscopically resected with “no significant damage to the ovary” per operative report.
At age 29, concerned about her future fertility, she presented to another fertility center with intent to freeze her eggs to preserve future fertility. She underwent a cycle of ovarian stimulation with gonadotropins. The cycle was, however, abandoned because of poor ovarian response. After subsequent blood testing, she was advised that “she was not a good candidate for fertility preservation because her FSH was high and her AMH was low.” Instead, she was advised to try to conceive as soon as possible “because, otherwise, her only chance of conception would be with donated eggs.”
The patient at that point was engaged, and she and her fiancé decided to proceed with infertility treatments. Over the ensuing 3 years, the couple underwent 4 IVF cycles in two different IVF centers. Oocyte yields were between 1 and 4, with only 2 cycles leading to embryo transfer of 1 and 2 embryos, respectively. The last advice she had received was to have surgery on both of her ovaries. She was warned that such surgery may castrate her, subsequently mandating use of donor eggs.
At presentation to CHR, the patient demonstrated multiple endometriomas in both ovaries, the largest 1.8 cm in diameter. Her FSH was 11.8 mIU/mL and her AMH was 0.6 ng/mL. Both ovaries, however, also demonstrates between 3 and 6 antral follicles. Free and total testosterone were both within the lowest 15th percentile of normal range, while her SHBG was relatively high at 115 nmol/L.
Analysis: This was a childless young woman who for most of her adult life had suffered from endometriosis. She now presented with at least stage III endometriosis and clear evidence of premature ovarian aging (POA), based on severe ovarian resistance to stimulation, high FSH and low AMH for her young age.
The patient was advised that, considering her young age, CHR’s published experience suggests that women with POA of here demonstrated severity with appropriate preparation and IVF cycle treatments still have excellent pregnancy and live birth chances. This patient’s case was, however, complicated by bilateral endometriomas, which created additional risks of leakage during egg retrieval that the patient had to be informed about. Moreover, presence of these endometriomas also, likely, reduced the number of oocytes that would be retrievable since some follicles would probably not be reachable during retrieval without risking entry by the retrieval needle into an endometrioma. Overall, the patient’s chances of conception with use of her own eggs were, therefore, assessed as moderate, and she was advised that her pregnancy and live birth chances would be better with use of donor eggs, which would also avoid the above-noted retrieval risks.
Resolution: The couple, nevertheless, decided to proceed with continuous use of the female’s own eggs. Following CHR’s specific protocol for women with low functional ovarian reserve (LFOR), the patient was pretreated with DHEA and CoQ10 supplementation until her testosterone levels had risen into approximately mid-range and her SHBG had fallen, which took approximately 6 weeks. Only at that point was a microdose-agonist IVF cycle initiated under maximal stimulation. Eight oocytes were retrieved, of which 7 were mature and 6 fertilized, resulting in 5 day-3 embryos. Two were transferred on day-3 and the remaining 3 embryos were cryopreserved.
The patient conceived and delivered a healthy female infant at term by Caesarean section (CS). Approximately nine months following her delivery, she underwent a frozen-thawed cycle with 2 surviving day-3 embryos but did not conceive.
At that point, her FSH was 12.2 mIU/ml and her AMH had declined to 0.4ng/mL. Her ovaries were prepared once again with DHEA and CoQ10 until androgens and SHBG were in range and, now 34 years old, she was stimulated in identical fashion as in her earlier retrieval cycle. She this time produced 7 oocytes and 4 embryos; two were transferred on day-3, and 2 were cryopreserved. She again conceived a singleton pregnancy and delivered a healthy male by CS.
Her 2 frozen embryos were thawed and transferred approximately a year later, leading to a third pregnancy and delivery, and a second female child.
Conclusions: This case, maybe to some extreme, demonstrates many of the typical problems encountered in infertile women with severe endometriosis. This patient, unquestionably, was very lucky in achieving in relatively short time so many pregnancies and deliveries. This, by no means, can be generalized, but it is also important to remember that pregnancy chances per embryo in young women are high and, therefore, young women do not need very large embryo numbers to achieve pregnancies.
The literature is split on whether egg quality in women with endometriosis is normal or lowered. The CHR experience suggests that both can be the case: Poor egg quality in endometriosis fertility patients is not usually associated with endometriosis itself but with the frequent co-morbidity of LFOR so often found in endometriosis patients, as in this case. If LFOR is properly addressed by preparing ovaries with DHEA and CoQ10 supplementation, egg quality can be surprisingly excellent, as this case also demonstrates.
This patient (and her then fiancé and now husband) are to be congratulated on reaching the best possible decision once the LFOR diagnosis became apparent. The couple’s IVF center, where this diagnosis was made after the patient did not respond as expected to stimulation of ovaries, is also to be applauded for abandoning egg freezing and advising the couple to try to conceive immediately.
Unfortunately, time was wasted during their 4 IVF cycles without proper preparation of the patient's ovaries. One would think that the concept of supplementing hypo-androgenic women with LFOR with DHEA (or testosterone directly) for approximately 6 weeks before IVF cycle start has by now already reached wider acceptance. Except in emergencies (for example, leakage of an endometrioma), CHR also disagrees with any form of ovarian surgery in women with severe endometriosis who are still desirous of pregnancy because, often, such surgery to significant degrees further reduces already low FOR, at times putting patients into menopause.
At least in this case, all ended well and, even though, as already noted, this couple was unusually lucky, their case is a good example for many important treatment principles that should be known by patients and physicians regarding endometriosis.
This is a part of the June 2017 issue of the VOICE.
Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned specialist in reproductive endocrinology, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.
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